August 24th, 2010
Study Suggests Prognostic Power of Dyspnea in Acute Heart Failure
Larry Husten, PHD
Results of a study with the hormone relaxin suggest that a lack of ongoing dyspnea relief may be an important predictor of outcome. Marco Metra and fellow investigators in the Pre-RELAX-AHF study randomized 232 patients with acute heart failure to placebo or one of 4 doses of relaxin. Only 25% of all patients in the study achieved early dyspnea relief, and patients who lacked persistent dyspnea relief and who had worsening heart failure had a longer length of initial hospital stay and a worse outcome at 60 days. The findings, conclude the authors in their report in the European Journal of Heart Failure, suggest that “beyond being the main measure” of acute heart failure symptoms, dyspnea endpoints “are also related to prognosis and hence may be regarded as important and meaningful targets of therapy.”
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This study, not surprisingly, shows that patients with worsening heart failure (WHF) during hospitalization for acute decompensated heart failure are sicker and therefore have worse short and medium term outcomes. In a multivariable analysis, patients with WHF had worse renal function and lower serum sodium — both well established predictors of disease severity and adverse outcomes. Furthermore, an analysis of in-hospital medications shows that patients with WHF
received lower doses of loop diuretics and a higher proportion were treated with inotropes — presumably because of hypotension or worsening renal function that limited adequate medical treatment.
The authors suggest that relaxin might be a promising drug for the treatment ofacute heart failure since it resulted in an improvement in early dyspnea and adecrease in WHF. Several drugs, such as nesiritide (VMAC) and tolvaptan (EVEREST) have been shown to improve dyspnea relative to placebo in acute heart failure. However, none of these have yet been shown to improve long-term outcomes. Conversely, in the UNLOAD trial, ultrafiltration did not improve dyspnea at 48 hours relative to standard care but did reduce HF hospitalizations at 3 months. Thus, while relief of dyspnea remains an important goal of acute heart failure therapy, its validity as a therapeutic end-point to assess the efficacy of a new heart failure drug remains questionable.